精子发生过程中的精原分化和减数分裂启动受到许多基因的严格调控,包括编码miRNA生物发生的酶。然而,单个miRNA是否以及如何调节这些过程尚不清楚。这里,我们报道了miR-202,let-7家族的成员,通过调节许多基因的及时表达来防止精子发生中的早熟精原分化和减数分裂起始,包括STRA8和DMRT6等关键监管机构的监管机构。在miR-202敲除(KO)小鼠中,未分化的精原细胞池减少,伴随着生育率的年龄依赖性下降。在KO小鼠中,SYCP3、STRA8和DMRT6在野生型同窝动物中表达较早,Dmrt6mRNA是miR-202-5p的直接靶标。此外,KO精原干细胞在体外培养和诱导时也观察到了早熟的精原分化和减数分裂的启动。并可以通过击倒Dmrt6部分获救。因此,我们不仅证明miR-202是减数分裂起始的调节因子,而且还在基础调节网络中鉴定了一个以前未知的模块.
Spermatogonial differentiation and meiotic initiation during spermatogenesis are tightly regulated by a number of genes, including those encoding enzymes for miRNA biogenesis. However, whether and how single miRNAs regulate these processes remain unclear. Here, we report that miR-202, a member of the let-7 family, prevents precocious spermatogonial differentiation and meiotic initiation in spermatogenesis by regulating the timely expression of many genes, including those for key regulators such as STRA8 and DMRT6. In miR-202 knockout (KO) mice, the undifferentiated spermatogonial pool is reduced, accompanied by age-dependent decline of fertility. In KO mice, SYCP3, STRA8 and DMRT6 are expressed earlier than in wild-type littermates, and Dmrt6 mRNA is a direct target of miR-202-5p. Moreover, the precocious spermatogonial differentiation and meiotic initiation were also observed in KO spermatogonial stem cells when cultured and induced in vitro, and could be partially rescued by the knockdown of Dmrt6. Therefore, we have not only shown that miR-202 is a regulator of meiotic initiation but also identified a previously unknown module in the underlying regulatory network.